Project Details
Projekt
Metabolic Regulation of Probabilistic Axon Growth Leads to Robust Sex-Specific Brain Asymmetry and Behavior
Applicant
Gerit Linneweber, Ph.D.
Subject Area
Developmental Neurobiology
Term
since 2022
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 453877723
In sexually dimorphic species, males and females often exhibit qualitative behavioral differences, typically linked to courtship and reproduction. Beyond these, sex differences also manifest themselves in quantitatively distinct patterns of shared behaviors. In Drosophila melanogaster, both sexes perform visual fixation in a walking assay called Buridan’s paradigm, but females display more exploratory behavior, whereas males show stronger fixation. Remarkably, the inherently probabilistic development of a single contralaterally projecting neuron type ‒ the Dorsal Cluster Neurons (DCNs) ‒ determines these behavioral disparities by generating differences in asymmetry. During the first funding period, we discovered that males develop significantly higher DCN axonal asymmetry than females. Hence, the enhanced visual fixation in males may arise from a male-specific increase in developmental asymmetry of DCN branching. Our characterization of sex-specific developmental and behavioral differences led to a surprising hypothesis: a higher metabolic rate in females leads to larger body size and more DCN axons in both hemispheres; higher numbers of axons reduce the relative differences between left and right and thus reduce asymmetry. Developmental temperature directly regulates metabolism based on a quantitative relationship that has been described by our RobustCircuit collaborators in P4. Remarkably, we found that this quantitative relationship describes DCN asymmetry; specifically, an exponential metabolic model can predict DCN axon numbers within the regular temperature range, but at extreme temperatures, the sexual dimorphism diminishes. These findings lead to a new core hypothesis for P8: metabolic regulation affects DCN wiring precision and thus asymmetry and sex-specific behavioral differences. Based on the established quantitative relationship of temperature, metabolism, and body size, we will utilize sex, temperature, insulin signaling, and mRNA translation to investigate the importance of metabolic differences for brain wiring. Upon completion, this work will have tested and established causal links between metabolic regulation, probabilistic axon branching, and the robustness of asymmetry-based sex-specific behavioral differences.
DFG Programme
Research Units
Co-Investigator
Professor Dr. Peter Robin Hiesinger
